title: Lupus-like oral mucosal lesions in mercury-induced autoimmune response in Brown Norway rats.
abstract: BACKGROUND
  Administration of mercury at nontoxic doses induces systemic autoimmune disease in Brown Norway (BN) rats. The pathogenesis of lupus-like oral mucosal lesion by mercury-induced autoimmunity is still unclear, even though the oral mucosa is observed to be commonly affected in mercury-treated BN rats. In this study, we investigated the immunopathology of lupus-like oral mucosal lesions in a model of mercury-induced systemic autoimmunity.
  
  
  METHODS
  Brown Norway male rats were injected subcutaneously with either phosphate-buffered saline (control) or mercury at a dose of 1.0 mg per kilogram of body weight on days 0, 3, 5, and 7. Blood, kidney, and tongue samples were taken at various timepoints for evaluation by immunohistochemistry, RT-PCR, and lupus band test (LBT).
  
  
  RESULTS
  Oral mucosal lesions were classified according to three consecutive temporal phases on the basis of infiltration of immunocompetent cells as follows: (phase I) infiltration of MHC class II+ dendritic cells (DC) and macrophages; (phase II) addition of ED1+ macrophage infiltrates; and (phase III) focal infiltration of pan T cells following increased infiltration of DC and macrophages. Dense infiltration of DC and macrophages was observed in the basement membrane (BM) zone of the oral epithelium. Tissue expression of IL-4 mRNA was detected in early lesions (phase I), suggesting that locally produced IL-4 may be responsible for Th2-mediated immune response. A linear and continuous smooth pattern of fluorescence was observed in the oral epithelial BM in addition to renal glomeruli, indicating immune complex deposits.
  
  
  CONCLUSIONS
  Local autoimmune responses are involved in the pathogenesis of mercury-induced lupus-like lesions of the oral mucosa.
authors.affiliation: Department of Morphological Biology, Division of Pathology, Fukuoka Dental College, 2-15-1 Tamura, Fukuoka, Japan. johno@college.fdcnet.ac.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Seno
authors.forename: Jun
authors.initials: J
authors.lastname: Ohno
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ota
authors.forename: Takao
authors.initials: T
authors.lastname: Hirofuji
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018956:CD5 Antigens / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004848:Epithelium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008628:Mercury; D009061:Mouth Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014059:Tongue / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D018956:CD5 Antigens; D000949:Histocompatibility Antigens Class II; D015847:Interleukin-4; D007371:Interferon-gamma; D008628:Mercury